Initial opioid prescription characteristics and risk of opioid misuse, poisoning and dependence: retrospective cohort study.

OBJECTIVE: To identify individual and initial prescription-related factors associated with an increased risk for opioid-related misuse, poisoning and dependence (MPD) in patients with non-cancer pain. METHODS: Cohort study linking several databases covering 5 million inhabitants of the region of Valencia, Spain, including all adults initiating prescription opioids in the period 2012-2018. To ascertain the association between the characteristics of the initial prescription choice and the risk of opioid MPD, we used shared frailty Cox regression models. We additionally considered death as a competing risk in sensitivity analyses. RESULTS: 958 019 patients initiated opioid prescription from 2012 to 2018, of which 0.13% experienced MPD. Most patients were prescribed tramadol as initial opioid (76.7%) followed by codeine (16.3%), long-acting opioids (6.7%), short-acting opioids (0.2%) and ultrafast opioids (0.1%). Initiation with ultrafast (HR 7.2; 95% CI 4.1 to 12.6), short-acting (HR 4.8; 95% CI 2.3 to 10.2) and long-acting opioids (HR 1.5; 95% CI 1.2 to 1.9) were associated with a higher risk of MPD when compared with tramadol. Initial prescriptions covering 4-7 days (HR 1.3; 95% CI 1.0 to 1.8), 8-14 days (HR 1.4; 95% CI 1.0 to 1.9), 15-30 days (HR 1.7; 95% CI 1.2 to 2.3) and more than one a month (HR 1.8; 95% CI 1.3 to 2.5) were associated with more MPD risk than initial prescriptions for 1-3 days. Treatments with >120 daily morphine milligram equivalents (MME) increased MPD risk (vs <50 MME, HR 1.6; 95% CI 1.1 to 2.2). Main individual factors associated with increased risk of MPD risk were male sex (HR 2.4; 95% CI 2.1 to 2.7), younger age (when compared with patients aged 18-44 years, patients aged 45-64 years, HR 0.4; 95% CI 0.4 to 0.5; patients aged 65-74 years, HR 0.4; 95% CI 0.3 to 0.5 and patients aged 75 years old and over, HR 0.7; 95% CI 0.6 to 0.8), lack of economic resources (2.1; 95% CI 1.8 to 2.5) and registered misuse of alcohol (2.9; 95% CI 2.4 to 3.5). Sensitivity analyses yielded overall comparable results. CONCLUSIONS: Our study identifies riskier patterns of opioid prescription initiation for non-cancer indications, as well as patient subgroups with higher risk of misuse, poisoning and dependence.

Estimating disease incidence rates and transition probabilities in elderly patients using multi-state models: a case study in fragility fracture using a Bayesian approach.

BACKGROUND: Multi-state models are complex stochastic models which focus on pathways defined by the temporal and sequential occurrence of numerous events of interest. In particular, the so-called illness-death models are especially useful for studying probabilities associated to diseases whose occurrence competes with other possible diseases, health conditions or death. They can be seen as a generalization of the competing risks models, which are widely used to estimate disease-incidences among populations with a high risk of death, such as elderly or cancer patients. The main advantage of the aforementioned illness-death models is that they allow the treatment of scenarios with non-terminal competing events that may occur sequentially, which competing risks models fail to do. METHODS: We propose an illness-death model using Cox proportional hazards models with Weibull baseline hazard functions, and applied the model to a study of recurrent hip fracture. Data came from the PREV2FO cohort and included 34491 patients aged 65 years and older who were discharged alive after a hospitalization due to an osteoporotic hip fracture between 2008-2015. We used a Bayesian approach to approximate the posterior distribution of each parameter of the model, and thus cumulative incidences and transition probabilities. We also compared these results with a competing risks specification. RESULTS: Posterior transition probabilities showed higher probabilities of death for men and increasing with age. Women were more likely to refracture as well as less likely to die after it. Free-event time was shown to reduce the probability of death. Estimations from the illness-death and the competing risks models were identical for those common transitions although the illness-death model provided additional information from the transition from refracture to death. CONCLUSIONS: We illustrated how multi-state models, in particular illness-death models, may be especially useful when dealing with survival scenarios which include multiple events, with competing diseases or when death is an unavoidable event to consider. Illness-death models via transition probabilities provide additional information of transitions from non-terminal health conditions to absorbing states such as death, what implies a deeper understanding of the real-world problem involved compared to competing risks models.

Real-world patterns of opioid therapy initiation in Spain, 2012-2018: A population-based, retrospective cohort study with 957,080 patients and 1,509,488 initiations.

Introduction: Europe has seen a steady increase in the use of prescription opioids, especially in non-cancer indications. Epidemiological data on the patterns of use of opioids is required to optimize prescription. We aim to describe the patterns of opioid therapy initiation for non-cancer pain and characteristics of patients treated in a region with five million inhabitants in the period 2012 to 2018. Methods: Population-based retrospective cohort study of all adult patients initiating opioid therapy for non-cancer pain in the region of Valencia. We described patient characteristics at baseline and the characteristics of baseline and subsequent treatment initiation. We used multinominal regression models to identify individual factors associated with initiation. Results: A total of 957,080 patients initiated 1,509,488 opioid treatments (957,080 baseline initiations, 552,408 subsequent initiations). For baseline initiations, 738,749 were with tramadol (77.19%), 157,098 with codeine (16.41%) 58,436 (6.11%) with long-acting opioids, 1,518 (0.16%) with short-acting opioids and 1,279 (0.13%) with ultrafast drugs. When compared to tramadol, patients initiating with short-acting, long-acting and ultrafast opioids were more likely to be older and had more comorbidities, whereas initiators with codeine were more prone to be healthier and younger. Treatments lasting less than 7 days accounted for 41.82% of initiations, and 11.89% lasted more than 30 days. 19.55% of initiators with ultrafast fentanyl received more than 120 daily Morphine Milligram Equivalents (MME), and 16.12% of patients initiating with long-acting opioids were prescribed more than 90 daily MME (p < 0.001). Musculoskeletal indications accounted for 65.05% of opioid use. Overlap with benzodiazepines was observed in 24.73% of initiations, overlap with gabapentinoids was present in 11.04% of initiations with long-acting opioids and 28.39% of initiators with short-acting opioids used antipsychotics concomitantly. In subsequent initiations, 55.48% of treatments included three or more prescriptions (vs. 17.60% in baseline initiations) and risk of overlap was also increased. Conclusion: Opioids are initiated for a vast array of non-oncological indications, and, despite clinical guidelines, short-acting opioids are used marginally, and a significant number of patients is exposed to potentially high-risk patterns of initiation, such as treatments lasting more than 14 days, treatments surpassing 50 daily MMEs, initiating with long-acting opioids, or hazardous overlapping with other therapies.

Impact of Three Safety Interventions Targeting Off-Label Use of Immediate-Release Fentanyl on Prescription Trends: Interrupted Time Series Analysis.

Background: The Spanish health authorities are concerned by the off-label use of immediate-release formulations of fentanyl (IRF) in noncancer pain and cancer pain in patients with no chronic pain therapy. Aim: To evaluate the impact of different interventions to improve appropriateness of IRF prescription on off-label prescription. Patients and methods: We used interrupted time series (ITS) to estimate immediate and trend changes of IRF prescription for noncancer pain (NCP) and breakthrough cancer pain (BCP) in patients with and without chronic cancer pain therapy associated with two medication reviews (I1 and I2) and the issue of a safety warning letter (I3) with data from a Spanish region with 5 million inhabitants, from 2015 to 2018. Results: The use of IRF for NCP in the region Valencia was reduced from about 1,800 prescriptions per week to around 1,400. The first medication review was followed by an immediate level change of -192.66 prescriptions per week (p < 0.001) and a downward trend change of -6.75 prescriptions/week (p < 0.001), resulting in a post-intervention trend of -1.99 (p < 0.001). I2 was associated with a trend change of -23.07 (p < 0.001) prescriptions/week. After I3, the trend changed markedly to 27.23 additional prescriptions/week, for a final post-intervention trend of 2.17 (p < 0.001). Controlled-ITS provided comparable results. For potentially inappropriate BCP use, the second medication review was followed by a downward, immediate level change of -10.10 prescriptions/week (p = 0.011) and a trend change of 2.31 additional prescriptions/week (p < 0.001) and the issue of the safety warning (I3) was followed by a downward trend change of -2.09 prescriptions/week (p = 0.007). Conclusion: Despite IRF prescription for NCP decreased, the interventions showed modest and temporary effect on off-label prescription. Our results call for a review of the design and implementation of safety interventions addressing inappropriate opioid use.

Association of Vitamin K and Non-Vitamin K Oral Anticoagulant Use and Cancer Incidence in Atrial Fibrillation Patients.

The association between the use of vitamin K antagonists (VKAs) and cancer risk reduction remains unclear. We aimed to assess the association between the use of VKAs or direct oral anticoagulants (DOACs) and the incidence of cancer in a large cohort of patients with atrial fibrillation (AF) by means of a population-based, propensity-weighted cohort study using population-wide databases including patients diagnosed with nonvalvular AF (NVAF) followed for up of 5 years (median 2.94 years). We created two cohorts based on the initiation therapy (VKA or DOAC). Initiation with VKA or DOAC was defined as filling a prescription with no previous exposure in the preceding 12 months. Cancer diagnoses of any type and for specific tumors (lung, colon, prostate, bladder, and breast). We included 39,989 patients, 31,200 (78.0%) in the VKA cohort. Incidence rate for any cancer was 12.45 per 1,000 person-year in the DOAC cohort vs. 14.55 in the VKA cohort (adjusted hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.02-1.32). In secondary outcomes, no differences were found for specific types of cancer, such as lung (HR: 1.28, CI: 0.89-1.83), colon (HR: 0.84, CI: 0.62-1.13), prostate (HR: 1.40, CI: 0.94-2.10), bladder (HR: 1.07, CI: 0.76-1.52), and breast (HR: 1.05, CI: 0.66-1.69). Sensitivity analyses yielded similar results. Subgroup analyses also produced consistent findings, except for men, for whom VKA was associated with a lower risk of colon cancer (HR: 0.68, 95% CI: 0.48-0.96). Our results do not confirm a chemoprotective effect of VKA when compared with DOAC in a large, real-world cohort of patients with NVAF followed for up to 5 years.

Treatment patterns and appropriateness of antipsychotic prescriptions in patients with schizophrenia.

Schizophrenia is a chronic mental condition presenting a wide range of symptoms. Although it has a low prevalence compared to other mental conditions, it has a negative impact on social and occupational functions. This study aimed to assess the appropriateness of antipsychotic medications administered to schizophrenic patients and describe current treatment patterns for schizophrenia. A retrospective cohort study was conducted in all patients over the age of 15 with an active diagnosis of schizophrenia and treated with antipsychotics between 2008 and 2013 in the Valencia region. A total of 19,718 patients were eligible for inclusion. The main outcome assessed was inappropriateness of the pharmacotherapeutic management, including polypharmacy use. Altogether, 30.4% of patients received antipsychotic polypharmacy, and 6.8% were prescribed three or more antipsychotics. Overdosage affected 318 individuals (1.6%), and 21.5% used concomitant psychotropics without an associated psychiatric diagnosis. Women and people with a comorbid condition like anxiety or depression were less likely to receive antipsychotic polypharmacy. In contrast, increased polypharmacy was associated with concomitant treatment with other psychoactive drugs, and only in user on maintenance therapy, with more visits to the mental health hospital. Overall, we observed a high level of inappropriateness in antipsychotic prescriptions. Greater adherence to guidelines could maximize the benefits of antipsychotic medications while minimizing risk of adverse effects.

Impact of Drug Safety Warnings and Cost-Sharing Policies on Osteoporosis Drug Utilization in Spain: A Major Reduction But With the Persistence of Over and Underuse. Data From the ESOSVAL Cohort From 2009 to 2015.

Background: Recent studies in several countries show a significant decrease in the consumption of osteoporosis drugs from a peak around 2009, mainly attributed to bisphosphonate safety warnings issued by regulatory agencies on jaw osteonecrosis, atypical fractures, and esophageal cancer, but no studies have assessed the impact of these warnings by risk of fracture strata. Aim: The aim of this work is to assess changes in the utilization of osteoporosis drugs in the region of Valencia (Spain) after safety warnings from regulatory agencies and cost-sharing changes, according to patient socio-demographic and risk of fracture characteristics. Patients and Methods: We constructed a monthly series of osteoporosis drug consumption for 2009-2015 from the ESOSVAL cohort (n = 11,035; women: 48%; mean age: 65 years old) and used interrupted time series and segmented linear regression models to assess changes in osteoporosis drug utilization while controlling for previous levels and trends after three natural intervention dates: the issue of the Spanish Agency for Drugs and Medical Products (AEMPS) Osteonecrosis Jaw Warning (Sept 2009), the AEMPS Atypical femur Fracture Warning (Apr 2011), and the modification of the cost-sharing scheme (Jul 2012). Results: The AEMPS Osteonecrosis Jaw Warning was not associated with a decline in the consumption of osteoporosis drugs, while the warning on atypical fracture (a downward trend of 0.11% fewer people treated each month) and the increase in the cost-sharing scheme (immediate change level of -1.07% in the proportion of people treated) were associated with a strong decline in the proportion of patients treated, so that by the end of 2015 osteoporosis drug consumption was around half that of 2009. The relative decline was similar in people with both a high and low risk of fracture. Conclusion: The AEMPS Atypical femur Fracture Warning of Apr 2010 was associated with a significant decrease in the number of people treated, reinforced by the increase in the pharmaceutical cost-sharing in 2012. Decreases in treatment affected patients both at a low and higher risk of fracture.

Primary Nonadherence to Oral Anticoagulants in Patients with Atrial Fibrillation: Real-World Data from a Population-Based Cohort.

BACKGROUND: Primary nonadherence (not filling a first prescription) is an important yet unstudied aspect of adherence to oral anticoagulant (OAC) therapy. OBJECTIVE: To estimate the rates of primary nonadherence to OACs and determine associated factors in real-world practice. METHODS: This population-based retrospective cohort study set in the Valencia region of Spain (about 5 million inhabitants) included all patients with atrial fibrillation who were newly prescribed OACs during 2011-2014 (N = 18,715). Primary nonadherence was obtained by linking electronic prescription and dispensing data and assessed by type of OAC-vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs). Covariates were obtained from diverse databases, including electronic medical records. Multivariate logistic regression models were used to assess characteristics associated with primary nonadherence, adjusting for a propensity score to minimize confounding by indication. RESULTS: Primary nonadherence to OACs was 5.62% (VKA 4.29% vs. NOAC 10.81%; P < 0.001), with varying rates among specific drugs (acenocoumarol 4.2%, warfarin 10.9%, apixaban 5.0%, dabigatran 7.9%, and rivaroxaban 15.5%). After adjusting for potential confounders, the likelihood of not filling the first prescription was higher for NOAC patients than for VKA patients (OR = 2.76, 95% CI = 2.41-3.15). High coinsurance in the older groups (OR = 2.63, 95% CI = 1.47-4.69 for patients aged 66-75 years and OR = 3.02, 95% CI = 1.58-5.76 for patients aged > 75 years); being a non-Spanish European (OR = 1.49, 95% CI = 1.12-1.99); and having dementia (OR = 1.72, 95% CI = 1.37-2.16) were positively associated with primary nonadherence. Electronic transmission of prescriptions (OR = 0.85, 95% CI = 0.74-0.96); liver disease (OR = 0.73, 95% CI = 0.54-0.99); and polypharmacy (OR = 0.59, 95% CI = 0.50-0.70) were inversely associated with primary nonadherence. CONCLUSIONS: Overall, primary nonadherence to OACs was relatively low (5%). However, important differences were found between VKAs and NOACs. After adjustment, patients prescribed NOACs nearly tripled the likelihood of nonadherence compared with patients prescribed VKAs, which could negatively affect their effectiveness in clinical practice. Identified correlates were similar to those shown in the limited evidence for other medications. DISCLOSURES: This work was partially supported by the 2013 Collaboration Agreement between the Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO) from the Valencia Ministry of Health and Boehringer Ingelheim, a nonconditioned program to conduct independent research in chronic health care, pharmacoepidemiology, and medical practice variation. Rodriguez-Bernal was funded by the Instituto de Salud Carlos III, Spanish Ministry of Health, and cofinanced by the European Regional Development Fund (grant number RD12/0001/0005). The views presented here are those of the authors and not necessarily those of the FISABIO Foundation, the Valencia Ministry of Health, or the study sponsors. The funding sources had no access to study data and did not participate in any way in the design or conduct of the study, data analysis, decisions regarding the dissemination of findings, the development of the manuscript, or its publication. Peiró has received fees for participation in scientific meetings and courses sponsored by Novartis and Ferrer International. In 2014, Sanfélix-Gimeno participated in an advisory meeting of Boehringer Ingelheim. García-Sempere is a former employee of Boehringer Ingelheim. Rodriguez-Bernal and Hurtado have no relationships relevant to the contents of this article to disclose. This work was previously submitted as an abstract (podium presentation) at the 31st International Society of Pharmacoepidemiology (ISPE) Annual Conference; August 22-26, 2015; Boston, Massachusetts.

Impact on the population of different bone mineral density testing criteria and appropriateness of densitometries in the ESOSVAL cohort, Spain.

CONTEXT: There is little consensus regarding which individuals should be recommended for bone mineral density (BMD) testing, a situation that could eventually affect the appropriateness of routine clinical practice. OBJECTIVES: The aim of this study was to estimate the impact on the population of the application of the BMD testing criteria provided by the National Osteoporosis Guideline Group (NOGG), National Osteoporosis Foundation (NOF), and Osteoporosis Canada and to assess the appropriateness of the BMD tests currently performed. DESIGN: A cross-sectional study was conducted using the baseline data of the ESOSVAL cohort. PARTICIPANTS: Participants included 11 035 men and women aged 50 years old and over attending primary health care centers in the Valencia region, Spain (2009-2010). MAIN OUTCOME AND MEASURES: BMD testing by dual-energy X-ray absorptiometry was recorded. RESULTS: Of the 10 710 people included in the study, 1617 (15.1%; 95% confidence interval [CI]: 14.4-15.8) received a BMD test. When applying the NOGG criteria, BMD testing would be recommended in 17.4% (95% CI: 16.7-18.1) of individuals, whereas this percentage would rise to 74.6% (95% CI: 73.7-75.4) and 80.1% (95% CI: 79.4-80.9) when using the Osteoporosis Canada and the NOF criteria, respectively. Regarding the appropriateness of the BMD tests performed in the ESOSVAL cohort, 40.7% (95% CI: 38.3-43.1), 86.0% (95% CI: 84.3-87.7), and 82.2% (95% CI: 80.3-84.1) of individuals having a BMD test met the NOGG, NOF, and the Canadian guidelines criteria, respectively. Of the tests performed, 40.7% would be deemed as appropriate, whereas 10.7% would be considered inappropriate. CONCLUSIONS: The impact on the population of the different recommendations is enormous, varying from 17% to 80% of the population over 50 who would be tested. Although in men it seems that a clinical rationale exists between the presence of risk factors and the rates of BMD testing, this pattern does not seem to exist in women. One in 10 of the densitometric tests performed were inappropriate according to all the guidelines.

Burden of disease assessment with summary measures of population health for the Region of Valencia, Spain: a population-based study.

BACKGROUND AND OBJECTIVE: An important input to decision-making and health planning is a consistent and comparative description of the population health status. The purpose of this study was to describe the burden of disease in the Region of Valencia (Spain). MATERIAL AND METHODS: Disability-adjusted life years (DALYs) were calculated and divided into years of life lost (YLLs) and years lived with disability (YLDs). Using death registry data and Valencian population estimates in 2008, we calculated the number of deaths and YLLs. YLDs were based on age- and sex-specific data for countries of the EURO-A subregional level (which includes the Region of Valencia) from the Global Burden of Disease study. The results were stratified by age group, sex and underlying cause of death. The DALY values were used to rank the leading conditions of disease burden. RESULTS: In 2008, the total number of DALYs lost was about 551 thousands (53% in men). The main categories of DALYs lost were neuropsychiatric conditions (30%; 167 thousands), malignant tumors (15%; 85 thousands), cardiovascular diseases (13%; 72 thousands) and sense organ diseases (8%; 46 thousands). Depression (8% of DALYs; 47 thousands), dementias (8%; 42 thousands), ischaemic heart disease (5%; 27 thousands), hearing loss (4%; 22 thousands), stroke (4%; 20 thousands) and lung cancer (3%; 19 thousands) were the leading specific causes of disease burden. CONCLUSIONS: We provide for the first time ever information on the burden of disease in the Valencian population. At this local level, the use of DALYs can help to monitor the population health status and guide the debates on rational priority-setting.

Carpal tunnel release surgery: small-area variation and impact of ambulatory surgery in the autonomous region of Valencia, Spain.

OBJECTIVE: This study aimed to analyze variability in rates of carpal tunnel release surgery among the healthcare areas of the autonomous region of Valencia, and to evaluate the contribution of ambulatory surgery and referrals to private hospitals to the variability found. METHODS: We carried out a cross-sectional, population-based study, describing the rates of carpal tunnel release surgery, standardized by age and sex, among areas in the region of Valencia in 2006. The observed variation was then analyzed using small-area analysis methods. Data from hospital admissions, referrals to private hospitals, population statistics and hospital resources were used to construct standardized rates, and Spearman's correlation was used to test the association with surgical setting and hospital resources. RESULTS: There were 8.2 carpal tunnel release surgeries per 10,000 inhabitants in the region of Valencia in 2006. Most (88.2%) of these interventions were performed as ambulatory surgery. After we excluded areas outside the 5th-95th percentiles, variation among areas was moderate and was similar for men and women. Variation was not associated with the proportion of the distinct surgical settings (admission to a public hospital, outpatient clinic, or referral to a private hospital) used in each area, or with the availability of resources. CONCLUSIONS: Variation in carpal tunnel release surgery among areas in the region of Valencia is moderate, but has a strong impact on the population because of the high prevalence of this disorder. This variation is not explained by the hospital resources available in each area or the surgical setting.

[Characterization of folate supplementation in pregnancy, based on a combination of health information systems]. / Caracterización de la suplementación de folatos en el embarazo a partir de la combinación de sistemas de información sanitaria.

OBJECTIVES: To explore the utility of combining health information systems from the Valencia Health Agency to characterize folate supplementation in pregnant women in the autonomous region of Valencia (Spain). METHODS: The cohort comprised women who gave birth during 2009 in hospitals within the Valencian Health Agency. These women were retrospectively followed-up using ABUCASIS electronic medical records and the GAIA electronic prescription system to identify folate consumption in the 3 months before and after conception. RESULTS: In 2009, there were 38,069 births in hospitals of the Valencian Health Agency, of which 37,040 (97.3%) were included for analysis. In 34% of women, at least one folate dispensation was registered with an official prescription form within the periconceptional period (6.6% in the 3 months prior to conception). Dispensation with an official prescription form was associated with older women, free pharmaceutical prescriptions, birth in Spain, antiepileptic medications, and a diagnosis of diabetes. Eight percent of women (23.6% of the folate-treated women) received folates at high doses. CONCLUSIONS: Folate consumption during pregnancy is systematically under-registered by healthcare information systems because health professionals do not use the official prescription form for prescription and dispensation. Database linkage is an inadequate approach to assess folic acid supplementation during pregnancy.

Timing of surgery for hip fracture and in-hospital mortality: a retrospective population-based cohort study in the Spanish National Health System.

BACKGROUND: While the benefits or otherwise of early hip fracture repair is a long-running controversy with studies showing contradictory results, this practice is being adopted as a quality indicator in several health care organizations. The aim of this study is to analyze the association between early hip fracture repair and in-hospital mortality in elderly people attending public hospitals in the Spanish National Health System and, additionally, to explore factors associated with the decision to perform early hip fracture repair. METHODS: A cohort of 56,500 patients of 60-years-old and over, hospitalized for hip fracture during the period 2002 to 2005 in all the public hospitals in 8 Spanish regions, were followed up using administrative databases to identify the time to surgical repair and in-hospital mortality. We used a multivariate logistic regression model to analyze the relationship between the timing of surgery (< 2 days from admission) and in-hospital mortality, controlling for several confounding factors. RESULTS: Early surgery was performed on 25% of the patients. In the unadjusted analysis early surgery showed an absolute difference in risk of mortality of 0.57 (from 4.42% to 3.85%). However, patients undergoing delayed surgery were older and had higher comorbidity and severity of illness. Timeliness for surgery was not found to be related to in-hospital mortality once confounding factors such as age, sex, chronic comorbidities as well as the severity of illness were controlled for in the multivariate analysis. CONCLUSIONS: Older age, male gender, higher chronic comorbidity and higher severity measured by the Risk Mortality Index were associated with higher mortality, but the time to surgery was not.

[Pharmaceutical prescription in primary care. SESPAS report 2012]. / La prescripción farmacéutica en atención primaria. Informe SESPAS 2012.

In 2010, the Spanish National Health Service (NHS) paid for 958 million prescriptions. Given the massive population exposure to medication, the risks associated with drug consumption are highly significant from the perspective of public health. Areas requiring improvement in primary care prescription include overtreatment of patients in low risk situations, undertreatment of those in whom medication is indicated, poor patient information, polymedication, self-medication and the appreciable percentage of preventable adverse effects. Surprisingly, most of the pharmaceutical strategies in the NHS have not aimed to address these problems but have instead concentrated on reducing pharmaceutical expenditure, which is not a problem of pharmaceutical expenditure per se but is rather a consequence of "the problems" of prescription (and of the regulation and management of pharmaceutical services). Some key elements to improve this situation include more integrated healthcare, the development of electronic medical records systems, overall strategies to improve safety, and reducing the role of the pharmaceutical industry. Macro strategies include creating an agency able to objectively assess the additional value provided by a new drug and its additional cost, price fixing in line with cost-effectiveness, and exclusion of drugs with little or no added value from coverage, etc. Managing prescription involves the development of longitudinal patient care programs that incorporate clinical actions from different professionals, including whom to treat, how much to treat and how to treat.

Are prescribing doctors sensitive to the price that their patients have to pay in the Spanish National Health System?

BACKGROUND: This study aims to design an empirical test on the sensitivity of the prescribing doctors to the price afforded for the patient, and to apply it to the population data of primary care dispensations for cardiovascular disease and mental illness in the Spanish National Health System (NHS). Implications for drug policies are discussed. METHODS: We used population data of 17 therapeutic groups of cardiovascular and mental illness drugs aggregated by health areas to obtain 1424 observations ((8 cardiovascular groups * 70 areas) + (9 psychotropics groups * 96 areas)). All drugs are free for pensioners. For non-pensioner patients 10 of the 17 therapeutic groups have a reduced copayment (RC) status of only 10% of the price with a ceiling of €2.64 per pack, while the remaining 7 groups have a full copayment (FC) rate of 40%. Differences in the average price among dispensations for pensioners and non-pensioners were modelled with multilevel regression models to test the following hypothesis: 1) in FC drugs there is a significant positive difference between the average prices of drugs prescribed to pensioners and non-pensioners; 2) in RC drugs there is no significant price differential between pensioner and non-pensioner patients; 3) the price differential of FC drugs prescribed to pensioners and non-pensioners is greater the higher the price of the drugs. RESULTS: The average monthly price of dispensations to pensioners and non-pensioners does not differ for RC drugs, but for FC drugs pensioners get more expensive dispensations than non-pensioners (estimated difference of €9.74 by DDD and month). There is a positive and significant effect of the drug price on the differential price between pensioners and non-pensioners. For FC drugs, each additional euro of the drug price increases the differential by nearly half a euro (0.492). We did not find any significant differences in the intensity of the price effect among FC therapeutic groups. CONCLUSIONS: Doctors working in the Spanish NHS seem to be sensitive to the price that can be afforded by patients when they fill in prescriptions, although alternative hypothesis could also explain the results found.